Melanocytes are present in the basal epidermis of skin, and play a role in producing a melanin pigment by external factors such as UV, transferring the produced melanin pigment to peripheral keratinocytes, thereby inhibiting DNA damage of the keratinocytes. However, the activity of these melanocytes is abnormally regulated by genetic factors, hormones and various disease factors, resulting in excessive pigmentation and hyperplasia beyond the normal level of pigment production, thereby leading to hyperpigmentation disorders such as freckles or lentigines or contributing as a factor for hypopigmentation disorders such as vitiligo.
The activation of excessive melanocytes is a state in which the homeostasis is lost in melanin pigment production due to chronic exposure of external stimuli such as ultraviolet rays. The skin is an elaborately regulated-immune system, and secretes a variety of cytokines, chemokines and other inflammatory mediators. The ultraviolet rays stimulate immune cells constituting the skin such as keratin-forming cells, macrophages, T cells and the like to induce the secretion of immune substances. Such immune substances not only create a chronic inflammatory state by accumulating immune cells to the microenvironment surrounding the periphery of the melanocytes, but also have an effect on the melanocytes themselves such as proliferation and migration of the melanocytes, and excessive production of melanin pigment.
Generally, it is well known that a cytokine, which is known as an immunological mediator, plays an important role in skin physiology such as atopic dermatitis and contact dermatitis, while a cytokine, which is an immunoreactive mediator with a small size of about 8 to 14 kD, shows a selective chemotaxis to surrounding cells, and has a function of inducing migration of cell and accumulation in a target organ, is not well known for its role in skin physiology. Similarly, studies on various immune substances have been conducted for an immuno-modulating therapy to regulate hyperpigmentation disorders caused by hyperactivation of melanocytes, but the direct influence of ITAC, which is a skin immune cell-derived factor and a chemokine, on melanocytes is not well known.
Immune responses caused by infections or internal or external injuries are well known for very precise control mechanisms. However, if a problem arises in the ability to precisely control the immune system, a chronic inflammation will occur, and such changes in the microenvironment will affect the activity of the surrounding cells.
Recently, it has been reported that the change in the cytokine mediating the immune response modifies the epigenetic pattern, thereby modifying the genes. And research on the treatment of chronic inflammation and further on the treatment of cancer caused by the the inflammation is actively carried out through epigenetic control substances. However, symptomatic genetic approaches to the melanocytes themselves or cells surrounding microenvironment regulation by the chemokine are a nonexistent state.